Pancreaze Information
Pancreaze (Pancreatic) Indications And Usage
Pancreaze (Pancreatic) (pancrelipase) is indicated for the treatment of exocrine pancreatic insufficiency due to cystic fibrosis or other conditions.
Pancreaze (Pancreatic) Dosage And Administration
Pancreaze (Pancreatic) is not interchangeable with other pancrelipase products.
Pancreaze (Pancreatic) is orally administered. Therapy should be initiated at the lowest recommended dose and gradually increased. The dosage of Pancreaze (Pancreatic) should be individualized based on clinical symptoms, the degree of steatorrhea present, and the fat content of the diet (see below).
Dosage recommendations for pancreatic enzyme replacement therapy were published following the Cystic Fibrosis Foundation Consensus Conferences. Pancreaze (Pancreatic) should be administered in a manner consistent with the recommendations of the Conferences provided in the following paragraphs. Patients may be dosed on a fat ingestion-based or actual body weight-based dosing scheme.
Pancreaze (Pancreatic) Dosage Forms And Strengths
The active ingredient in Pancreaze (Pancreatic) evaluated in clinical trials is lipase. Pancreaze (Pancreatic) is dosed by lipase units.
Pancreaze (Pancreatic) is available in 4 color coded capsule strengths.
Other active ingredients include protease and amylase. Each Pancreaze (Pancreatic) capsule strength contains the specified amounts of lipase, protease, and amylase as follows:
Pancreaze (Pancreatic) Contraindications
Pancreaze (Pancreatic) Warnings And Precautions
Fibrosing colonopathy has been reported following treatment with different pancreatic enzyme products. Fibrosing colonopathy is a rare serious adverse reaction initially described in association with high-dose pancreatic enzyme use, usually with use over a prolonged period of time and most commonly reported in pediatric patients with cystic fibrosis. The underlying mechanism of fibrosing colonopathy remains unknown. Doses of pancreatic enzyme products exceeding 6,000 lipase units/kg of body weight per meal have been associated with colonic strictures in children less than 12 years of age.Patients with fibrosing colonopathy should be closely monitored because some patients may be at risk of progressing to stricture formation. It is uncertain whether regression of fibrosing colonopathy occurs. It is generally recommended, unless clinically indicated, that enzyme doses should be less than 2,500 lipase units/kg of body weight per meal (or less than 10,000 lipase units/kg of body weight per day) or less than 4,000 lipase units/g fat ingested per day
Doses greater than 2,500 lipase units/kg of body weight per meal (or greater than 10,000 lipase units/kg of body weight per day) should be used with caution and only if they are documented to be effective by 3-day fecal fat measures that indicate a significantly improved coefficient of fat absorptionPatients receiving higher doses than 6,000 lipase units/kg of body weight per meal should be examined and the dosage either immediately decreased or titrated downward to a lower range.
Pancreaze (Pancreatic) Adverse Reactions
The most serious adverse reactions reported with different pancreatic enzyme products of the same active ingredient (pancrelipase) include fibrosing colonopathy, hyperuricemia and allergic reactions
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
The short-term safety of Pancreaze (Pancreatic) was assessed in two clinical trials conducted in 57 patients with exocrine pancreatic insufficiency (EPI) due to CF. Study 1 was conducted in 40 patients, ages 8 years to 57 years; Study 2 was conducted in 17 patients, ages 6 to 30 months. In Study 1, Pancreaze (Pancreatic) was administered in a dose of approximately 6,300 lipase units per kilogram per day for lengths of treatment ranging from 8 to 26 days; in Study 2, Pancreaze (Pancreatic) was administered in four treatment arms (doses of 1,375, 2,875, 4,735, and 5,938 lipase units per kilogram per day) for lengths of treatment ranging from 6 to 11 days. The population was nearly evenly distributed in gender, and approximately 96% of patients were Caucasian.
Study 1 was a randomized, double-blind, placebo-controlled, study of 40 patients, ages 8 to 57 years, with EPI due to CF. In this study, patients received Pancreaze (Pancreatic) at individually titrated doses (not to exceed 2,500 lipase units per kilogram per meal) for 14 days, followed by randomization to Pancreaze (Pancreatic) or matching placebo for 7 days of treatment. The mean exposure to Pancreaze (Pancreatic) during this study, including titration period and randomized withdrawal period, was 18 days.
The incidence of adverse events (regardless of causality) was higher during placebo treatment (60%) than during Pancreaze (Pancreatic) treatment (40%). The most common adverse events reported during the study were gastrointestinal complaints, which were reported more commonly during placebo treatment (55%) than during Pancreaze (Pancreatic) treatment (30%). The type and incidence of adverse events were similar in children (8 to 11 years), adolescents (12 to 17 years), and adults (greater than 18 years).
Table 1 enumerates treatment-emergent adverse events that occurred in at least 2 patients (greater than or equal to 10%) treated with either Pancreaze (Pancreatic) or placebo in Study 1. Adverse events were classified by Medical Dictionary for Regulatory Activities (MedDRA) terminology.
Study 2 was a randomized, investigator-blinded, dose-ranging study of 17 patients, ages 6 to 30 months, with EPI due to CF. All patients were transitioned from their usual PEP treatment to Pancreaze (Pancreatic) at 375 lipase units per kilogram body weight per meal for a 6 day run-in period. Patients were then randomized to receive Pancreaze (Pancreatic) at one of four doses (375, 750, 1,125, and 1,500 lipase units per kilogram body weight per meal) for 5 days. Adverse events were collected on patient diary entries and at each study visit.
The most commonly reported adverse events were gastrointestinal, including diarrhea and vomiting, and were similar in type and frequency across treatment arms and to those reported in the double-blind, placebo-controlled trial (Study 1).
Post-marketing data for Pancreaze (Pancreatic) has been available since 1988. The safety data is similar to that described below.
Delayed- and immediate-release pancreatic enzyme products with different formulations of the same active ingredient (pancrelipase) have been used for the treatment of patients with exocrine pancreatic insufficiency due to cystic fibrosis and other conditions, such as chronic pancreatitis. The long-term safety profile of these products has been described in the medical literature. The most serious adverse events included fibrosing colonopathy, distal intestinal obstruction syndrome (DIOS), recurrence of pre-existing carcinoma, and severe allergic reactions including anaphylaxis, asthma, hives, and pruritus. The most commonly reported adverse events were gastrointestinal disorders, including abdominal pain, diarrhea, flatulence, constipation and nausea, and skin disorders including pruritus, urticaria and rash. In general, these products have a well defined and favorable risk-benefit profile in exocrine pancreatic insufficiency.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Pancreaze (Pancreatic) Drug Interactions
No drug interactions have been identified. No formal interaction studies have been conducted.
Pancreaze (Pancreatic) Use In Specific Populations
The short-term safety and effectiveness of Pancreaze (Pancreatic) were assessed in two clinical studies in pediatric patients with EPI due to CF; one study included patients ages 6 to 30 months, and the other included patients ages 8 years to 17 years.
Study 1 was a randomized, double-blind, placebo-controlled study in 40 patients, 14 of whom were pediatric patients, including 7 children aged 8 to 11 years, and 7 adolescents aged 12 to 17 years. The safety and efficacy in pediatric patients in this study were similar to adult patients ].
Study 2 was a randomized, investigator-blinded, dose-ranging study in 17 pediatric patients aged 6 to 30 months. When patient regimen was switched from their usual PEP regimen to Pancreaze (Pancreatic) , patients showed similar control of their fat malabsorption .
The safety and efficacy of pancreatic enzyme products with different formulations of pancrelipase consisting of the same active ingredient (lipases, proteases, and amylases) for treatment of children with exocrine pancreatic insufficiency due to cystic fibrosis has been described in the medical literature and through clinical experience.
Dosing of pediatric patients should be in accordance with recommended guidance from the Cystic Fibrosis Foundation Consensus Conferences Doses of other pancreatic enzyme products exceeding 6,000 lipase units/kg of body weight per meal have been associated with fibrosing colonopathy and colonic strictures in children less than 12 years of age
Pancreaze (Pancreatic) Overdosage
In Study 1, a 10 year-old patient was administered a Pancreaze (Pancreatic) dose of 12,399 lipase units per kilogram per day for the duration of the open-label and randomized withdrawal periods. The patient experienced mild abdominal pain throughout both study periods. Abnormal chemistry data at the end of the study included mild elevations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and serum phosphate. Abnormal hematology data at the end of the study included mild elevations of hematocrit. No abnormalities from analyses of urinalysis or uric acid were noted.
Chronic high doses of pancreatic enzyme products have been associated with fibrosing colonopathy and colonic strictures . High doses of pancreatic enzyme products have been associated with hyperuricosuria and hyperuricemia, and should be used with caution in patients with a history of hyperuricemia, gout, or renal impairment .
Pancreaze (Pancreatic) Description
Pancreaze (Pancreatic) is a pancreatic enzyme preparation consisting of pancrelipase, an extract derived from porcine pancreatic glands. Pancrelipase contains multiple enzyme classes, including porcine-derived lipases, proteases, and amylases.
Each capsule for oral administration contains enteric-coated microtablets that are each approximately 2 mm in diameter.
The active ingredient evaluated in clinical trials is lipase. Pancreaze (Pancreatic) is dosed by lipase units. Other active ingredients include protease and amylase.
Inactive ingredients in Pancreaze (Pancreatic) include cellulose, colloidal anhydrous silica, crospovidone, magnesium stearate, methacrylic acid ethyl acrylate copolymer, montan glycol wax, simethicone emulsion, talc and triethyl citrate.
Pancreaze (Pancreatic) is available in four color coded strengths. Each Pancreaze (Pancreatic) capsule strength contains the specified amounts of lipase, protease, and amylase as follows:
Pancreaze (Pancreatic) Clinical Studies
The short-term safety and efficacy of Pancreaze (Pancreatic) were evaluated in two studies conducted in 57 patients with exocrine pancreatic insufficiency (EPI) associated with cystic fibrosis (CF).
Study 1 was a randomized, double-blind, placebo-controlled study of 40 patients, ages 8 to 57 years, with EPI due to CF. In this study, patients received Pancreaze (Pancreatic) at individually titrated doses (not to exceed 2,500 lipase units per kilogram per meal) for 14 days (open label period) followed by randomization to Pancreaze (Pancreatic) or matching placebo for 7 days of treatment (double-blind withdrawal period). Only patients with coefficient of fat absorption (CFA) ≥80% in the open label period were randomized to the double-blind withdrawal period. The mean dose during the controlled treatment period was 6,400 lipase units per kilogram per day. All patients consumed a high-fat diet (greater than or equal to 100 grams of fat per day) during the treatment period.
The primary efficacy endpoint was the change in CFA from the open label period to the end of the double-blind withdrawal period. The CFA was determined by a 72-hour stool collection period during both treatment periods, when both fat excretion and fat ingestion were measured (Table 2).
At the end of the double-blind withdrawal period, the mean change in CFA from the open label period to the end of the double-blind withdrawal period was -2% with Pancreaze (Pancreatic) treatment compared to -34% with placebo treatment. There were similar responses to Pancreaze (Pancreatic) by age and gender.
Study 2 was a randomized, investigator-blinded, dose-ranging study of 17 patients, ages 6 months to 30 months (mean 18 months) with EPI due to CF. The final analysis population was limited to 16 patients; 1 patient was excluded due to withdrawal of consent. All patients were transitioned from their usual PEP treatment to Pancreaze (Pancreatic) at 375 lipase units per kilogram body weight per meal for a 6 day run-in period. Patients were then randomized to receive Pancreaze (Pancreatic) at one of four doses (375, 750, 1,125, and 1,500 lipase units per kilogram body weight per meal) for 5 days. The CFA was measured at the end of the run-in period and at the end of the randomized period (Table 3).
Overall, patients showed similar CFA at the end of the run-in period (mean Pancreaze (Pancreatic) dose of 1,600 lipase units per kilogram body weight per day) as at the end of the study across the four treatment arms.
Pancreaze (Pancreatic) How Supplied/storage And Handling
Pancreaze (Pancreatic) (pancrelipase) Delayed-Release Capsules
4,200 USP units of lipase; 10,000 USP units of protease; 17,500 USP units of amylase.
Pancreaze (Pancreatic) (pancrelipase) is supplied as hard gelatin capsules with a yellow opaque body and clear cap imprinted with "McNEIL" and "MT 4" and packaged in bottles of 100–(NDC 50458-341-60).
Pancreaze (Pancreatic) (pancrelipase) Delayed-Release Capsules
10,500 USP units of lipase; 25,000 USP units of protease; 43,750 USP units of amylase.
Pancreaze (Pancreatic) (pancrelipase) is supplied as hard gelatin capsules with a pink opaque body and clear cap imprinted with "McNEIL" and "MT 10" and packaged in bottles of 100–(NDC 50458-342-60).
Pancreaze (Pancreatic) (pancrelipase) Delayed-Release Capsules
16,800 USP units of lipase; 40,000 USP units of protease; 70,000 USP units of amylase.
Pancreaze (Pancreatic) (pancrelipase) is supplied as hard gelatin capsules with a salmon opaque body and clear cap imprinted with "McNEIL" and "MT 16" and packaged in bottles of 100–(NDC 50458-343-60).
Pancreaze (Pancreatic) (pancrelipase) Delayed-Release Capsules
21,000 USP units of lipase; 37,000 USP units of protease; 61,000 USP units of amylase.
Pancreaze (Pancreatic) (pancrelipase) is supplied as hard gelatin capsules with a white opaque body and cap imprinted with "McNEIL" and "MT 20" and packaged in bottles of 100–(NDC 50458-346-60).
Avoid heat. Pancreaze (Pancreatic) hard gelatin capsules should be stored in a dry place in the original container. After opening, KEEP THE CONTAINER TIGHTLY CLOSED between uses to PROTECT FROM MOISTURE. Do not store above 25°C (77°F).
The Pancreaze (Pancreatic) 4200 USP Units of lipase bottle contains a desiccant packet. DO NOT eat or throw away the packet (desiccant) in your medicine bottle. This packet will protect your medicine from moisture.
Keep out of reach of children.
DO NOT CRUSH Pancreaze (Pancreatic) delayed-release capsules or the capsule contents.
Pancreaze (Pancreatic) Patient Counseling Information
See
Manufactured by:
Manufactured for:
©Ortho-McNeil-Janssen Pharmaceuticals, Inc. 2010
Pancreaze (Pancreatic) Medication Guide
Read this Medication Guide before you start taking Pancreaze (Pancreatic) and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about your medical condition or treatment.
Take Pancreaze (Pancreatic) exactly as prescribed by your doctor. Do not take more or less Pancreaze (Pancreatic) than directed by your doctor.
Pancreaze (Pancreatic) is a prescription medicine used to treat people who cannot digest food normally because their pancreas does not make enough enzymes due to cystic fibrosis or other conditions. Pancreaze (Pancreatic) may help your body use fats, proteins, and sugars from food.
Pancreaze (Pancreatic) contains a mixture of digestive enzymes including lipases, proteases, and amylases from pig pancreas.
Pancreaze (Pancreatic) is safe and effective in children when taken as prescribed by your doctor.
Know the medicines you take. Keep a list of them and show it to your doctor and pharmacist when you get a new medicine.
Call your doctor right away if you have any of these symptoms.
Pancreaze (Pancreatic) and other pancreatic enzyme products are made from the pancreas of pigs, the same pigs people eat as pork. These pigs may carry viruses. Although it has never been reported, it may be possible for a person to get a viral infection from taking pancreatic enzyme products that come from pigs.
Tell your doctor if you have any side effect that bothers you or does not go away.
These are not all the possible side effects of Pancreaze (Pancreatic) . For more information, ask your doctor or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
You may also report side effects to McNeil Pediatrics at 1-800-526-7736.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Pancreaze (Pancreatic) for a condition for which it was not prescribed. Do not give Pancreaze (Pancreatic) to other people to take, even if they have the same symptoms you have. It may harm them.
This Medication Guide summarizes the most important information about Pancreaze (Pancreatic) . If you would like more information, talk to your doctor. You can ask your pharmacist or doctor for information about Pancreaze (Pancreatic) that is written for healthcare providers.
For more information go to or call 1-800-526-7736 (Monday - Friday 9am to 5pm EST).
Active Ingredient: lipase, protease, amylase
Inactive Ingredients: cellulose, colloidal anhydrous silica, crospovidone, magnesium stearate, methacrylic acid ethyl acrylate copolymer, montan glycol wax, simethicone emulsion, talc and triethyl citrate. The capsule shell contains gelatin, titanium dioxide, sodium lauryl sulfate, sorbitan monolaurate, and gelatin capsule imprint ink. Pancreaze (Pancreatic) 4,200, 10,500, and 16,800 USP Units of lipase also contain iron oxide.
Nordmark Arzneimittel GmbH & Co. KG 25436 Uetersen, Germany.
McNeil Pediatrics, Division of Ortho-McNeil-Janssen Pharmaceuticals, Inc. Titusville, NJ 08560.
Revised: April 2010
©Ortho-McNeil-Janssen Pharmaceuticals, Inc. 2010
Pancreaze (Pancreatic)
Pancreaze (Pancreatic)
